BLOCKING OF CUE-INDUCED DRUG REINSTATEMENT

• US 20150051192A1
• Filed: 03/25/2013
• Published: 02/19/2015
• Est. Priority Date: 03/27/2012
• Status: Abandoned Application

• Current Assignee: Albany Medical College (Albany Medical Center)
• Original Assignee: Albany Medical College (Albany Medical Center)
• Inventors: Glick, Stanley D., Polston, James E.
• Application Number:
  US14/387,339
• Publication Number:
  US 20150051192A1
• Time in Patent Office: Days
• US Class Current: 514/214.02
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 25/34 Tobacco-abuse
• CPC Class Codes: A61P 25/36 Opioid-abuse

Abstract

A method of preventing drug use relapse by administering an effective amount of an α3β4 nicotinic antagonist to a mammal after an initial period of drug use, and preventing a relapse of drug use. A method of preventing drug use relapse due to cue inducement by administering an effective amount of an α3β4 nicotinic antagonist to a mammal after an initial period of drug use, and preventing a relapse of drug use during cue inducement. A method of preventing drug use relapse due to cue inducement by modulating the dopaminergic mesolimbic pathway by blocking α3β4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala of a mammal after an initial period of drug use, and preventing a relapse of drug use during cue inducement. A method of preventing drug use relapse by preventing a relapse of drug use during cue inducement.

Claims

1. A method of preventing drug use relapse, including the steps of:

administering an effective amount of an α

3β

4 nicotinic antagonist to a mammal after an initial period of drug use; and

preventing a relapse of drug use.

2. The method of claim 1, wherein the α

3β

4 nicotinic antagonist is a coronaridine congener.

3. The method of claim 2, wherein the coronaridine congener is chosen from the group consisting of 18-hydroxycoronaridine;

18-hydroxyvoacangine;

18-hydroxyconopharyngine;

16-ethoxycarbonyl-18-hydroxyibogamine;

16-ethoxycarbonyl-18-hydroxyibogaine;

16-ethoxycarbonyl-18-hydroxyibogaline;

16-hydroxymethyl-18-hydroxyibogamine;

16-hydroxymethyl-18-hydroxyibogaine;

16-hydroxymethyl-18-hydroxyibogaline;

18-methoxycoronaridine;

18-methoxyvoacangine;

18-methoxyconopharyngine;

16-ethoxycarbonyl-18-methoxyibogamine;

16-ethoxycarbonyl-18-methoxyibogaine;

16-ethoxycarbonyl-18-methoxyibogaline;

16-hydroxymethyl-18-methoxyibogamine;

16-hydroxymethyl-18-methoxyibogaine;

16-hydroxymethyl-18-methoxyibogaline;

18-benzyloxycoronaridine;

18-benzyloxyvoacangine;

18-benzyloxyconopharyngine;

16-ethoxycarbonyl-18-benzyloxyibogamine;

16-ethoxycarbonyl-18-benzyloxyibogaine;

16-ethoxycarbonyl-18-benzyloxyibogaline;

18-hydroxycoronaridine laurate;

18-hydroxyvoacangine laurate;

18-hydroxyconopharyngine laurate;

16-ethoxycarbonyl-18-hydroxyibogamine laurate;

16-ethoxycarbonyl-18-hydroxyibogaine laurate;

16-ethoxycarbonyl-18-hydroxyibogaline laurate;

18-hydroxycoronaridine acetate;

18-hydroxyvoacangine acetate;

18-hydroxyconopharyngine acetate;

16-ethoxycarbonyl-18-hydroxyibogamine acetate;

16-ethoxycarbonyl-18-hydroxyibogaine acetate;

16-ethoxycarbonyl-18-hydroxyibogaline acetate;

18-hydroxycoronaridine methoxyethoxymethyl ether;

18-hydroxyvoacangine methoxyethoxymethyl ether;

18-hydroxyconopharyngine methoxyethoxymethyl ether;

16-ethoxycarbonyl-18-hydroxyibogamine methoxyethoxymethyl ether;

16-ethoxycarbonyl-18-hydroxyibogaine methoxyethoxymethyl ether;

16-ethoxycarbonyl-18-hydroxyibogaline methoxyethoxymethyl ether; and

pharmaceutically acceptable salts thereof.

4. The method of claim 1, further including the step of indirectly modulating the dopaminergic mesolimbic pathway via blockade of α

3β

4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala.

5. The method of claim 1, wherein said administering step is further defined as administering the α

3β

4 nicotinic antagonist by intraperitoneal injection in a dose of 0.05 mg/kg to 200 mg/kg.

6. The method of claim 1, wherein the drug is chosen from the group consisting of a barbiturate, morphine, codeine, heroin, levorphanol, meperidine, methadone, propoxyphene, acetylmethadol (LAAM), pentazocine, butorphanol, nalbuphine, buprenorphine, dezocine, fentanyl, d-amphetamine, 1-amphetamine, d1-amphetamine, methamphetamine, 3,4-methylenedioxy-N-methylamphetamine (MDMA) benzphetamine, phentermine, diethylpropion, phenmetrazine, phendimetrazine, chlorphentermine, clortermine, mazindol, phenylpropanolamine, cocaine, methylphenidate, nicotine, cathinone (khat plant), meprobamate, chlordiazepoxide, diazepam, oxazepam, lorazepam, flurazepam, prazepam, chlorazepate, alprazolam, triazolam, temazepam, halazepam, quadazepam, midazolam, estazolam, ethanol, pentobarbital, phenobarbital, secobarbital, amobarbital, delta-9-tetrahydrocannabinol (THC), combinations thereof, analogs thereof, and derivatives thereof.

7. A method of preventing drug use relapse due to cue inducement, including the steps of:

administering an effective amount of an α

3β

4 nicotinic antagonist to a mammal after an initial period of drug use; and

preventing a relapse of drug use during cue inducement.

8. The method of claim 7, wherein the α

3β

4 nicotinic antagonist is a coronaridine congener.

9. The method of claim 8, wherein the coronaridine congener is chosen from the group consisting of 18-hydroxycoronaridine;

18-hydroxyvoacangine;

18-hydroxyconopharyngine;

16-ethoxycarbonyl-18-hydroxyibogamine;

16-ethoxycarbonyl-18-hydroxyibogaine;

16-ethoxycarbonyl-18-hydroxyibogaline;

16-hydroxymethyl-18-hydroxyibogamine;

16-hydroxymethyl-18-hydroxyibogaine;

16-hydroxymethyl-18-hydroxyibogaline;

18-methoxycoronaridine;

18-methoxyvoacangine;

18-methoxyconopharyngine;

16-ethoxycarbonyl-18-methoxyibogamine;

16-ethoxycarbonyl-18-methoxyibogaine;

16-ethoxycarbonyl-18-methoxyibogaline;

16-hydroxymethyl-18-methoxyibogamine;

16-hydroxymethyl-18-methoxyibogaine;

16-hydroxymethyl-18-methoxyibogaline;

18-benzyloxycoronaridine;

18-benzyloxyvoacangine;

18-benzyloxyconopharyngine;

16-ethoxycarbonyl-18-benzyloxyibogamine;

16-ethoxycarbonyl-18-benzyloxyibogaine;

16-ethoxycarbonyl-18-benzyloxyibogaline;

18-hydroxycoronaridine laurate;

18-hydroxyvoacangine laurate;

18-hydroxyconopharyngine laurate;

16-ethoxycarbonyl-18-hydroxyibogamine laurate;

16-ethoxycarbonyl-18-hydroxyibogaine laurate;

16-ethoxycarbonyl-18-hydroxyibogaline laurate;

18-hydroxycoronaridine acetate;

18-hydroxyvoacangine acetate;

18-hydroxyconopharyngine acetate;

16-ethoxycarbonyl-18-hydroxyibogamine acetate;

16-ethoxycarbonyl-18-hydroxyibogaine acetate;

16-ethoxycarbonyl-18-hydroxyibogaline acetate;

18-hydroxycoronaridine methoxyethoxymethyl ether;

18-hydroxyvoacangine methoxyethoxymethyl ether;

18-hydroxyconopharyngine methoxyethoxymethyl ether;

16-ethoxycarbonyl-18-hydroxyibogamine methoxyethoxymethyl ether;

16-ethoxycarbonyl-18-hydroxyibogaine methoxyethoxymethyl ether;

16-ethoxycarbonyl-18-hydroxyibogaline methoxyethoxymethyl ether; and

pharmaceutically acceptable salts thereof.

10. The method of claim 7, wherein the drug is chosen from the group consisting of a barbiturate, morphine, codeine, heroin, levorphanol, meperidine, methadone, propoxyphene, acetylmethadol (LAAM), pentazocine, butorphanol, nalbuphine, buprenorphine, dezocine, fentanyl, d-amphetamine, 1-amphetamine, d1-amphetamine, methamphetamine, 3,4-methylenedioxy-N-methylamphetamine (MDMA) benzphetamine, phentermine, diethylpropion, phenmetrazine, phendimetrazine, chlorphentermine, clortermine, mazindol, phenylpropanolamine, cocaine, methylphenidate, nicotine, cathinone (khat plant), meprobamate, chlordiazepoxide, diazepam, oxazepam, lorazepam, flurazepam, prazepam, chlorazepate, alprazolam, triazolam, temazepam, halazepam, quadazepam, midazolam, estazolam, ethanol, pentobarbital, phenobarbital, secobarbital, amobarbital, delta-9-tetrahydrocannabinol (THC), combinations thereof, analogs thereof, and derivatives thereof.

11. The method of claim 7, wherein the cue is chosen from the group consisting of music, drugs, drug paraphernalia, seeing others using drugs, environments where drugs were consumed, environments where drugs are supplied, arousal, anxiety, and discomfort.

12. The method of claim 7, wherein said administration step is further defined as orally delivering the α

3β

4 nicotinic antagonist.

13. The method of claim 7, wherein said administration step is further defined as administering 0.05 mg/kg to 200 mg/kg of the α

3β

4 nicotinic antagonist.

14. The method of claim 7, wherein said administering step is further defined as administering the α

3β

4 nicotinic antagonist at a time period after drug use.

15. The method of claim 7, wherein said preventing step further includes the step of reducing conditioned place preference (CPP) of the mammal.

16. The method of claim 7, further including the step of indirectly modulating the dopaminergic mesolimbic pathway via blockade of α

3β

4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala.

17. A method of preventing drug use relapse due to cue inducement, including the steps of:

modulating the dopaminergic mesolimbic pathway by blocking α

3β

4 nicotinic receptors in the habenulo-interpeduncular pathway and the basolateral amygdala of a mammal after an initial period of drug use; and

preventing a relapse of drug use during cue inducement.

18. The method of claim 17, wherein the α

3β

4 nicotinic antagonist is a coronaridine congener chosen from the group consisting of 18-hydroxycoronaridine;

18-hydroxyvoacangine;

18-hydroxyconopharyngine;

16-ethoxycarbonyl-18-hydroxyibogamine;

16-ethoxycarbonyl-18-hydroxyibogaine;

16-ethoxycarbonyl-18-hydroxyibogaline;

16-hydroxymethyl-18-hydroxyibogamine;

16-hydroxymethyl-18-hydroxyibogaine;

16-hydroxymethyl-18-hydroxyibogaline;

18-methoxycoronaridine;

18-methoxyvoacangine;

18-methoxyconopharyngine;

16-ethoxycarbonyl-18-methoxyibogamine;

16-ethoxycarbonyl-18-methoxyibogaine;

16-ethoxycarbonyl-18-methoxyibogaline;

16-hydroxymethyl-18-methoxyibogamine;

16-hydroxymethyl-18-methoxyibogaine;

16-hydroxymethyl-18-methoxyibogaline;

18-benzyloxycoronaridine;

18-benzyloxyvoacangine;

18-benzyloxyconopharyngine;

16-ethoxycarbonyl-18-benzyloxyibogamine;

16-ethoxycarbonyl-18-benzyloxyibogaine;

16-ethoxycarbonyl-18-benzyloxyibogaline;

18-hydroxycoronaridine laurate;

18-hydroxyvoacangine laurate;

18-hydroxyconopharyngine laurate;

16-ethoxycarbonyl-18-hydroxyibogamine laurate;

16-ethoxycarbonyl-18-hydroxyibogaine laurate;

16-ethoxycarbonyl-18-hydroxyibogaline laurate;

18-hydroxycoronaridine acetate;

18-hydroxyvoacangine acetate;

18-hydroxyconopharyngine acetate;

16-ethoxycarbonyl-18-hydroxyibogamine acetate;

16-ethoxycarbonyl-18-hydroxyibogaine acetate;

16-ethoxycarbonyl-18-hydroxyibogaline acetate;

18-hydroxycoronaridine methoxyethoxymethyl ether;

18-hydroxyvoacangine methoxyethoxymethyl ether;

18-hydroxyconopharyngine methoxyethoxymethyl ether;

16-ethoxycarbonyl-18-hydroxyibogamine methoxyethoxymethyl ether;

16-ethoxycarbonyl-18-hydroxyibogaine methoxyethoxymethyl ether;

16-ethoxycarbonyl-18-hydroxyibogaline methoxyethoxymethyl ether; and

pharmaceutically acceptable salts thereof.

19. A method of preventing drug use relapse, including the step of:

preventing a relapse of drug use during cue inducement.